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Aims: The objective of this study was to investigate the association and combined prognostic significance of the PD-L1, Smoothened protein and β-catenin expressions in patients with clear cell renal cell carcinoma (ccRCC)., Methods: The PD-L1, Smoothened protein and β-catenin expression were evaluated in 104 ccRCC patients. All studied tumor samples were acquired from nephrectomy specimens of primary tumors and not from biopsies or metastases. An indirect immunohistochemistry using polyclonal rabbit anti-Smoothened antibody, monoclonal mouse anti-human β-catenin-1 antibody, immunohistochemical assay PD-L1 28-8 pharmDx using monoclonal rabbit anti-PD-L1 antibody and anti-VHL (C- terminal) rabbit antibody was used. Immunohistochemistry was scored semiquantitavely., Results: Median overall survival (OS) was significantly better in patients with lower PD-L1 expression (≤5%), Smoothened protein (SMO) expression (<5%) or cytoplasmic β-catenin expression (≤75%) than in patients with higher expressions of these biomarkers (P<0.001, P=0.047, and P<0.001, respectively). Membranous β-catenin showed an opposite effect with its lower expression (≤75%) being associated with longer OS (P=0.020). There was significant association between PD-1 and PD-L1 expression (P=0.007) and significant association of tumor grade (WHO 2016) with membranous β-catenin (P<0.001), cytoplasmic β-catenin (P=0.005), pVHL (P=0.042), PD-L1 (P=0.049) and PD-1 (P=0.028) expression., Conclusion: The present study provides the first data on the potential association and combined prognostic significance of frequency of primary cilia, PD-L1, Smoothened protein and β-catenin expression with the outcome in clear cell renal cell carcinoma., Competing Interests: The authors report no conflicts of interest in this work.

Branchioma is an uncommon benign neoplasm with an adult male predominance, typically occurring in the lower neck region. Different names have been used for this entity in the past (ectopic hamartomatous thymoma, branchial anlage mixed tumor, thymic anlage tumor, biphenotypic branchioma), but currently, the term branchioma has been widely accepted. Branchioma is composed of endodermal and mesodermal lineage derivatives, in particular epithelial islands, spindle cells, and mature adipose tissue without preexistent thymic tissue or evidence of thymic differentiation. Twenty-three branchiomas were evaluated morphologically. Eighteen cases with sufficient tissue were assessed by immunohistochemistry, next-generation sequencing (NGS) using the Illumina Oncology TS500 panel, and fluorescence in situ hybridization (FISH) using an RB1 dual-color probe. All cases showed a biphasic morphology of epithelial and spindle cells with intermingled fatty tissue. Carcinoma arising in branchioma was detected in three cases. The neoplastic cells showed strong AE1/3 immunolabeling (100%), while the spindle cells expressed CD34, p63, and SMA (100%); AR was detected in 40-100% of nuclei (mean, 47%) in 14 cases. Rb1 showed nuclear loss in ≥ 95% of neoplastic cells in 16 cases (89%), while two cases revealed retained expression in 10-20% of tumor cell nuclei. NGS revealed a variable spectrum of likely pathogenic variants (n = 5) or variants of unknown clinical significance (n = 6). Loss of Rb1 was detected by FISH in two cases. Recent developments support branchioma as a true neoplasm, most likely derived from the rudimental embryological structures of endoderm and mesoderm. Frequent Rb1 loss by immunohistochemistry and heterozygous deletion by FISH is a real pitfall and potential confusion with other Rb1-deficient head and neck neoplasms (i.e., spindle cell lipoma), especially in small biopsy specimens., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Branchioma (previously called ectopic hamartomatous thymoma, branchial anlage mixed tumor, or thymic anlage tumor) is a rare lower neck lesion with an adult male predominance and an uncertain histogenesis. Except for 4 cases, all branchiomas described in the literature were benign. Recently, HRAS mutation was detected in one case, but still little is known about the molecular genetic background of this rare entity. We herein report the histological, immunohistochemical, and molecular genetic analysis of a branchioma with a nested/organoid (neuroendocrine-like) morphology in a 78-year-old man. Histology revealed classical branchioma areas merging with nested/organoid cellular component lacking conventional features of malignancy. Immunohistochemistry was positive for high-molecular-weight cytokeratins. CD34 was expressed in the spindle cell component. Moreover, the tumor cells showed near-complete loss of retinoblastoma (RB1) expression (<1% of cells positive). All neuroendocrine markers (synaptophysin, chromogranin, and INSM1) were negative. Next-generation sequencing (TSO500 Panel) revealed 5 pathogenic/likely pathogenic mutations including 1 mutation in KRAS and 2 different mutations in each of MSH6 and PTEN. FISH and DNA sequencing were negative for RB1 gene alterations. To our knowledge, this is the first report of a branchioma showing misleading nested/organoid morphology and the first report on Rb1 immunodeficiency in this entity, in addition to multiple gene mutations revealed by NGS., (© 2023. The Author(s).)

Purpose: The aim of this study was to investigate the potential association and combined prognostic significance of the frequency of primary cilia (PC), programmed cell death protein-1 receptor (PD1) and CD8+ tumor infiltrating lymphocytes (TIL) in patients with clear cell renal cancer (ccRCC)., Methods: The frequency of PC, PD1 expression and the frequency of intratumoral CD8+ TIL were evaluated in 104 ccRCC patients., Results: The median frequency of PC was 0.003. The expression of PD1+ cells were <5% in 52 patients, 5-25% in 34 patients and 26-50% in 13 patients and >50% in 5 patients. Intratumoral CD8+ TIL were evaluable in all patients: negative in 1 patient, <25% in 63, 26-50% in 29 and >50% in 11 patients. Overall survival (OS) according to the frequency of PC was significantly shorter in patients with higher frequency (≥0.002) than in patients with lower frequency (<0.002) (p<0.001). Median OS was significantly shorter in patients with higher (25%) CD8+ TIL and higher (>25%) PD1+ expression than in patients with lower (<25%) expression (4.6 vs. 97. years, p=0.006 and 2.9 vs. 8.9 years, p=0.006, respectively)., Conclusions: The present study provides the first data on the potential association and combined prognostic significance of frequency of PC, PD1+ cells and CD8+ TIL in patients with clear cell renal cancer.

Introduction: Currently, the predominant question is whether a laparoscopic approach is comparatively radical in comparison with an open access approach, especially in the circumferential resection margin and quality of the completeness of total mesorectal excision. These factors are important in determining the quality of surgical care as well as long-term results of the treatment., Aim: This article focuses on the evaluation of circumferential resection margins and on the quality of mesorectal excision of middle and lower rectum tumors. In addition, laparoscopic and open techniques are compared., Material and Methods: Data were collected prospectively and stored in a rectal cancer registry over a 3-year period. The parameters studied were age, sex, body mass index, localization and topography of the tumor, clinical stage, neoadjuvant chemotherapy and its response, the type of surgery, character of the circumferential and distal margins, quality of the mesorectal excision, pT and pN., Results: One hundred and twenty-five patients were chosen for our study. Laparoscopy was performed in 53 operations and a conventional approach was performed in 72 operations. Complete mesorectal excision was achieved in 54.7% of laparoscopic operations versus 44.4% in the conventional technique; partially complete excision was performed in 20.8 and 12.5%, respectively. Incomplete excisions were described in 24.5 and 43.1% (p = 0.085). Positive circumferential margin occurred during laparoscopic surgery in 11 (20.8%) patients, and in the case of conventional resection in 27 (37.5%) patients (p = 0.044)., Conclusions: Our study showed comparable results between laparoscopic and open access procedures during rectal resection. The results achieved, in particular in the quality of the mesorectal excision and negative circumferential resection margin, show that the laparoscopic approach is comparable to conventional surgical techniques, with an adequate surgical outcome, in the treatment of rectal cancer.

The primary cilium is a solitary, sensory, non-motile microtubule-based structure that arises from the centrosome and is projected from the surface of most human cells. The objective of the current pilot study was to conduct an investigation of presence and frequency of cilia in gastrointestinal stromal tumors (GIST).The presence of primary cilia in GIST was evaluated in 9 patients, including 8 primary tumors and 1 liver metastasis. In 2 patients the presence of primary cilia was evaluated not only in the primary tumor, but also in recurrence: in 1 patient in recurrence without previous treatment with imatinib and in 1 patient in recurrence after treatment with imatinib. The primary cilia of GIST cells were immunofluorescently stained with primary monoclonal anti-acetylated tubulin alpha antibody and cell nuclei with DAPI.We observed 9985 nuclei of cells of GISTs and 425 primary cilia in total. The median of frequency of primary cilia in cells of GISTs in all examined samples was 4.26%, in primary tumors was 4.32% and in metastases was 3.64%, respectively. This pilot study provides the evidence of the presence of primary cilia in GISTs in different organs. Primary cilia were identified in all examined cases of GIST, including primary tumors, metastases and recurrent lesions without and with previous treatment with imatinib.

Low-grade myofibroblastic sarcoma (LGMS) is a very rare, atypical myofibroblastic tumor with fibromatosis-like features with predilection mostly in head and neck region. LGMS occurs primarily in adult patients with a slight male predominance. Only few cases of LGMS affecting the larynx have been reported in literature to this date. We describe a case of low-grade myofibroblastic sarcoma of the larynx in a 40-year-old male patient. The clinicopathological characteristics, immunohistochemical findings and treatment are discussed.

Introduction: Circumferential resection margin (pCRM) and the completeness of mesorectal excision (ME) are two independent prognostic factors significantly associated with the radicality of surgical treatment. Positive pCRM and incomplete mesorectal excision are associated with a significantly higher incidence of local recurrence and worse patient prognosis. The aim of this article is to analyze the risk factors associated with incomplete mesorectal excision., Material and Methods: Patients operated on at the Department of Surgery, University Hospital Hradec Kralove between January 2011 and February 2013 were included in the study. The patients data were prospectively collected and entered in the Dg C20 registry. The following factors were analyzed: sex, age, BMI, cN, pT, clinical stage, the involved segment of the rectum, neoadjuvant therapy, circumferential tumour location, the type of surgical approach and the type of surgery., Results: 168 patients were operated on during the above period. 9 (5.3%) palliative stomas and 159 (94.6%) resection procedures were performed in this group of 168 patients. 7 (4.4%) patients were excluded because the quality of excision was not assessed in them. 114 (75%) resections, including 5 intersphincteric resections, were performed in the group of the remaining 152 patients. 10 (7%) were Hartmanns procedures a 28 (18%) were amputation procedures. Out of 152 procedures, 69 (45%) were performed laparoscopically. Positive (y)pCRO was recorded in 26 (17%) patients, predominantly after abdominoperineal resection (APR) - 11 out of 27 (41%), and Hartmanns operation - 6 out of 10 (60%). Incomplete ME was observed in 45 patients (30%), complete ME in 81 patients (53%) and partially complete in 26 patients (17%). Univariate analysis confirmed statistically significant factors associated with incomplete mesorectal excision: (y)pT (P = 0.00027), type of surgery (P = 0.00001) and tumour location (P = 0.00001). Multivariate analysis then confirmed two independent prognostic factors associated with incomplete mesorectal excision. It was the location of the tumour in the distal third of the rectum and the (y)pT stage of the tumour., Conclusion: Distal rectum tumor location and higher (y)pT are associated with a higher risk of incomplete mesorectal excision with worse patient prognosis.

Introduction: The issue of achieving radical circumferential margin in laparoscopic rectal surgery has not yet been satisfactorily clarified. In this paper we have focused on circumferential margin assessment and the quality of the mesorectal excision, comparing laparoscopic and open resection for cancer of the middle and lower rectum., Material and Methods: The results of surgical procedures for middle and low rectal cancer were analysed. All the interventions were performed at the Department of Surgery, Teaching Hospital in Hradec Kralove, during the period from January 2011 to December 2012. The data were prospectively collected and entered in the Rectal Cancer Registry. Age, gender, BMI, tumour localisation and topography, the clinical stage, preoperative chemoradiotherapy and response to it, the type of surgery, distal and circumferential margin characteristics, mesorectal excision quality, pT and pN were compared for laparoscopic and open surgery., Results: A total of 161 patients were operated on for rectal cancer during the abovementioned period. 94 patients were included in the trial following selection. Laparoscopy was used in 40 patients and open surgery in 54 patients. Laparoscopic approach was performed in 33 (82.5%) low anterior resections (including four intersphincteric resections), 6 (15%) abdominoperineal amputations and 1 (2.5%) Hartmanns procedure. Open surgery was used for 26 (48.1%) low anterior resections, 21 (38.9%) APR and 7 (13%) Hartmanns procedures. Complete mesorectal excision was achieved in 45% of the laparoscopic resections vs. 46.3% of open resections. Nearly complete excision was performed in 22.5% and 11.1%, respectively. Finally, incomplete excision was described in 30% vs. 38.9%. No available data for TME was detected in three patients. The differences in TME were not statistically significant. Positive circumferential margin was found in 5 (12.5%) patients in the laparoscopy group; on the contrary, in the group undergoing open surgery, pCRO+ was found in 15 (27.8%) patients. Here, too, the results were not statistically significant. When patients without preoperative chemoradiotherapy were excluded, the relationship between ypCRM in the laparoscopy and open surgery group was on the border of statistical significance (Fischer=0.0556)., Conclusion: As has been shown in our trial, the outcomes of laparoscopic and open approach in rectal cancer treatment are very similar. Particularly, mesorectal excision quality and negative CRM results have proven that the laparoscopic technique is safe and comparable to open surgery in rectal cancer treatment.

The primary cilium is a mechanosensory, solitary, non-motile microtubule-based structure that in the quiescent phase of the cell cycle projects from the surface of the majority of human cells, including embryonal, stem and mesenchymal cells, fibroblasts, myoblasts, cardiomyocytes, vascular smooth muscle and endothelial cells. Primary cilia are in increased frequency also present on the surface of endothelial cells in atherosclerotic predilection sites, lipoid streaks and dots and atheromatous plaques. The primary cilium is formed from the mother centriole. Primary cilia are currently studied in mechanobiology of cardiovascular apparatus and their role in cell migration, cell cycle control and atherogenesis. The aim of this paper is to provide a review of the current knowledge on the primary cilia of cells of cardiovascular apparatus.

Background: Gastrointestinal stromal tumors (GISTs) may arise in any part of the gastrointestinal tract; extra-gastrointestinal locations are extremely rare. Only a few cases of extragastrointestinal stromal tumor arising from the pancreas were reported. None of the reports described a long-term follow-up of the patients., Method: This report describes an interesting and unusual case of GIST arising from the pancreas., Results: A 74-year-old female presented with a palpable abdominal mass. CT scan showed a large mass 11 x 8 x 4 cm originating from the tail of the pancreas. Percutaneous biopsy revealed a GIST predominantly with spindle cells, but some parts also contained epitheloid cells. The patient was treated by distal pancreatic resection with splenectomy. Immunohistochemistry of the tumor showed a staining pattern characteristic of GIST. The patient has achieved a long-term survival of five years and six months without any sign of recurrence of the disease., Conclusion: This is the first reported case of an extra-gastrointestinal stromal tumor arising from the pancreas treated surgically, with a long-term survival.

Abdominal liposarcoma is a rare tumor of uncertain prognosis. Radical surgery is possible in about two-thirds of the patients, and the prognosis of patients with inoperable tumors is dismal. Only a few cases of liposarcoma complicating pregnancy have been documented. We report a case of a patient who was diagnosed with metastatic abdominal liposarcoma during the third trimester of the pregnancy. After induced vaginal delivery, palliative surgery was performed and one cycle of systemic combination chemotherapy was administered. Despite the multimodality treatment the patient died of progressive disease within one month after diagnosis. Autopsy revealed high-grade pleomorphic liposarcoma arising from the retroperitoneum with liver and lung metastases.

Localization of hemangioma in retroperineum causes late diagnosis of the disease. The tumour is usually detected only when the clinical symptoms caused by the pressure of the surrounding tissues occur. This article presents the case of retroperitoneal hemangioma preoperatively diagnosed as suspect feochromocytoma.

Authors present the possibilities of different examination methods in cases of intraocular expansions and specific diagnostic methods to determine the actual etiology of the intraocular process in the posterior segment in particular. Of special concern to authors are cases, as is e.g. vitreous hemorrhage, in whose the standard examination methods are not useful. Pars plana vitrectomy with intraocular biopsy of the tissue for histological and cytological examination is very effective method to determine the proper diagnosis. The case report concerns with a 58 years old woman with vitreous hemorrhage and suspect tumor-like lesion, diagnosed by means of ultrasound examination. The pars plana vitrectomy revealed extensive preretinal organized hemorrhage with intravitreal hemorrhage. Samples for cytological examination were taken.

In this study was evaluated the rate of cytodiagnostic accuracy of Hashimoto's thyroiditis (HT) in smears prepared from thyroid fine-needle aspirates in 72 cases and of focal lymphocytic thyroiditis (FLT) in 101 cases. The cytodiagnostic accuracy of Hashimoto's thyroiditis (HT) was 75% and 20% in case of focal lymphocytic thyroiditis (FLT). In case of focal lymphocytic thyroiditis (FLT) the cytodiagnostics of autoimmune lymphocytic diseases of thyroid gland apears to have very low ability.

Acute spontaneous arterio-venous fistula complicating atherosclerotic abdominal aortic aneurysm (AAA) is rare. This life-threatening setting is observed in 1-2% of all AAAs and 2-4% of ruptured of AAAs. The triad of abdominal or lower back pain, pulsatile abdominal mass, and continual abdominal machinery-like bruit is seen only in half of cases. Currently, CT angiography is a noninvasive technique which enables a rapid and exact preoperative diagnosis. The authors describe three cases of aortoiliac aneurysm complicated by an acute arteriovenous fistula which were diagnosed using spiral CT.

A case is presented of a 70-year-old man treated for 3 months for necrotizing pancreatitis with multiorgan failure. The autopsy revealed enterococcal endocarditis affecting all eleven valvular cusps of the four heart valves.